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尼沃卢马布加上伊皮利穆马布治疗可能切除的肝细胞癌:长期疗效和生物标志物探索

Yih-Jyh Lin¹, Da-Liang Ou², Yung-Yeh Su³

¹Division of General and Transplant Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Liver Cancer Collaborative Oncology Group, National Cheng Kung University Hospital, Tainan, Taiwan.

Journal of hepatology

|September 19, 2025

概括

在手术前的新辅助尼沃卢马布加上伊皮利穆马布免疫疗法显示了在肝细胞癌 (HCC) 患者中改善长期生存的可行性和潜力. 免疫疗法诱导的三级淋巴体结构 (TLS) 与增强的抗瘤免疫力和治疗反应相关.

科学领域:

肝胆瘤学肝胆瘤学
免疫治疗是一种免疫疗法.
手术瘤学手术瘤学

背景情况:

肝细胞癌 (HCC) 管理受益于免疫检查点抑制剂 (ICI) 组合疗法.
新辅助或外科期间的ICI治疗可能会改善可切除的HCC的临床结果.
这项研究研究了尼沃卢马布加上伊皮利穆马布在潜在的切除性HCC中,探索预测生物标志物.

研究的目的:

评估新辅助药尼沃卢马布加上伊皮利穆马布在潜在可切除的HCC患者中的疗效和安全性.
为了确定可预测这种组合免疫疗法的治疗反应的生物标志物.
评估在新辅助免疫疗法后进行手术的可行性.

主要方法:

43名可能切除的HCC患者每3周接受尼沃卢马布 (3毫克/千克) 加上伊皮利穆马布 (1毫克/千克).
瘤反应在2个和4个周期后被评估,然后进行手术或替代治疗.
对瘤和血液样本进行了基因组,转录组和免疫细胞分析.

主要成果:

24名患者接受了手术;8名患者实现了重大病理反应 (>90%的瘤缩).
估计4年无进展生存率为44%,整体生存率为60%.
在瘤中增加的干扰素γ和三级淋巴体结构 (TLS) 信号与客观反应相关. 在小鼠模型中的B细胞枯竭取消了抗PD-1/抗CTLA-4的有效性,突出了TLS的作用. 外围T细胞激活/耗尽与反应和生存相关.

结论:

新辅助药尼沃卢马布加上伊皮利穆马布,然后进行手术是可行的,并可能改善潜在可切除的HCC的长期存活率.
免疫疗法诱导的TLS形成与增强的抗瘤免疫力有关.
监测外围T细胞耗尽可能预测免疫治疗反应.

关键词:

T细胞耗尽的情况树突细胞是一种树突细胞.这是一种新辅助剂.周围血液中的单核细胞.三级淋巴体结构的第三级淋巴体结构

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